chr6-22320271-C-T

Variant names:

• chr6-22320271-C-T
• rs10946546
• ENST00000561912.3:n.705+2473C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000561912.3(CASC15):​n.705+2473C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 148,072 control chromosomes in the GnomAD database, including 8,479 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8479 hom., cov: 32)
• Consequence: CASC15 ENST00000561912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.936
• Publications: 3 publications found

Genes affected

CASC15 (HGNC:28245): (cancer susceptibility 15) This gene produces a long non-coding RNA that may regulate cell proliferation. This RNA is upregulated in hepatocellular carcinoma, where it is thought to function as an oncogene. However, some splice variants of this gene may function as a tumor suppressor in neuroblastoma and other tumor types. Circular RNA variants were observed at this gene. [provided by RefSeq, Dec 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000561912.3	n.705+2473C>T		intron_variant	Intron 6 of 10	5
CASC15	ENST00000651569.1	n.641+2473C>T		intron_variant	Intron 6 of 7

Frequencies

GnomAD3 genomes AF: 0.310 AC: 45823 AN: 147956 Hom.: 8477 Cov.: 32

Gnomad AFR AF: 0.0850

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.331

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.310 AC: 45842 AN: 148072 Hom.: 8479 Cov.: 32 AF XY: 0.314 AC XY: 22678 AN XY: 72174

African (AFR) AF: 0.0848 AC: 3331 AN: 39284

American (AMR) AF: 0.336 AC: 4935 AN: 14672

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1237 AN: 3450

East Asian (EAS) AF: 0.402 AC: 2020 AN: 5030

South Asian (SAS) AF: 0.282 AC: 1268 AN: 4504

European-Finnish (FIN) AF: 0.447 AC: 4634 AN: 10372

Middle Eastern (MID) AF: 0.350 AC: 100 AN: 286

European-Non Finnish (NFE) AF: 0.405 AC: 27339 AN: 67530

Other (OTH) AF: 0.332 AC: 681 AN: 2052

Alfa AF: 0.331 Hom.: 1512

Bravo AF: 0.284

Asia WGS AF: 0.283 AC: 985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.33
PhyloP100		0.94

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10946546; hg19: chr6-22320500;